Early-phase Study of ART002g1 Injection in HeFH: Safety, Tolerability and Preliminary Efficacy

Early-phase Clinical Study on Safety, Tolerability and Preliminary Efficacy of ART002g1 Injection in the Treatment of Heterozygous Familial Hypercholesterolemia

This study is an open-label, single ascending dose (SAD) study designed to evaluate the safety and tolerability of ART002g1 in patients with heterozygous familial hypercholesterolemia (HeFH) who require further reduction in low-density lipoprotein cholesterol (LDL-C). ART002g1 uses base editing technology, which is designed to interfere with the expression of the PCSK9 gene in the liver, thereby reducing the circulating levels of PCSK9 and LDL-C. The primary objectives of this study are to determine the safety and pharmacodynamic (PD) profiles of ART002g1 in this patient population.

Subjects must meet all the following criteria to be eligible for enrollment:

1. Male or female, aged 18 to 70 years (inclusive) at the time of signing the Informed Consent Form (ICF);
2. Body weight between 45 and 90 kg (inclusive) at screening;
3. Definite diagnosis of heterozygous familial hypercholesterolemia (HeFH), meeting either of the following two criteria (1) or (2):

（1) HeFH diagnosed to be caused by mutations in the LDLR, APOB, or PCSK9 gene;

(2) Meeting 2 out of the 3 following criteria for adults per the Dutch Lipid Clinical Network (DLCN) criteria:

1. Serum LDL-C ≥ 4.7 mmol/L without prior lipid-lowering treatment;
2. Cutaneous or tendinous xanthomas, or arcus cornealis (in subjects < 45 years old);
3. Presence of FH or early-onset atherosclerotic cardiovascular disease (ASCVD) in first-degree relatives.

Subjects must not be enrolled if they meet any one or more of the following exclusion criteria:

1. Diagnosis of compound heterozygous FH, double heterozygous FH, or homozygous FH (HoFH);
2. Positive for hepatitis B surface antigen (HBsAg), or positive for hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA titer ≥ 1 × 10² copies/L; positive for hepatitis C virus (HCV) antibody with positive peripheral blood HCV RNA; positive for human immunodeficiency virus (HIV) antibody;
3. Any unstable systemic disease, including but not limited to: unstable angina; cerebrovascular accident or transient ischemic attack (within 6 months prior to screening); myocardial infarction (within 6 months prior to screening); history of heart failure (NYHA Class II-IV); severe arrhythmia requiring pharmacotherapy; liver, kidney, or metabolic diseases; or other unstable systemic diseases as determined by the investigator;
4. History of percutaneous transluminal coronary angioplasty (PTCA), percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG) within 6 months prior to the first dose; or documented severe coronary artery stenosis as confirmed by coronary CT or coronary angiography within 90 days prior to randomization.